Collagen is the most common structural protein in animals. It is also the most abundant protein in mammals as the main component of connective tissue. Collagen's basic elemental unit is the tropocollagen protein. Tropocollagen is composed of three polypeptide chains of the same size. These chains are wound about each other forming a superhelical cable or a triple-stranded helical rod.
To date, twenty eight types of collagen have been identified and described. The five most common types are types I-V. Collagen type I (Col1) is the most abundant collagen found in the supporting structure of skin tissue, tendon, bone and in the eye cornea. Collagen type II (Col2) is found primarily in particular cartilage, making up about 50% of all cartilage protein. Type III collagen (Col3) is found in many connective tissues throughout the body and its expression is increased during development as well as early in the healing process of a variety of tissues such as bone, tendon, ligament, and skin. Collagen type IV (Col4) is primarily found in basal lamina and eye lens. Collagen type V (Col5) is found in placenta and skin.
Breast cancer is the most frequently diagnosed cancer in women and is the leading cause of cancer-related deaths in women worldwide (World Health Organization: Latest World Cancer Statistics. 2013, Press Release Number 223, http://www.iarc.fr/en/media-centre/pr/2013/pdfs/pr223_E.pdf). In fact, more than 500,000 women are predicted to die in 2015 alone. Without major changes in prevention or treatment, those numbers are anticipated to nearly double in 20 years. In most patients, death is not caused by the primary tumor but rather by metastases. The extracellular matrix (ECM) of the tumor microenvironment plays a critical role in cancer development and progression through its ability to modulate physical, biochemical, and biomechanical cues perceived by both tumor cells and cancer associated stromal cells (Lu P et al., J Cell Biol 2012, 196:395-406; Dvorak H F et al., J Surg Oncol 2011, 103:468-474; Radisky E S et al., Rev Endocr Metab Disord 2007, 8:279-287). However, the mechanistic role that individual stromal components play in regulating tumor cell behavior is largely unknown.
As a major component of the ECM, collagen is increasingly recognized to play a key role in regulating breast cancer progression. While the majority of research on collagen in breast cancer has focused on Col1, and many reports have documented a negative correlation between Col1 expression and prognosis in breast cancer patients (Albini A et al., Cancer Metastasis Rev 2008, 27:75-83), collagens type IV, V, VI and XVIII have also been implicated in modulation of breast cancer cell activities and fate (Luparello C et al., J Carcinogene Mutagene 2013, S13-007; Lourenco G J et al., Breast Cancer Res Treat 2006, 100:335-338; Barsky S H et al., Am J Pathol 1982, 108:276-283; Robledo T et al., Matrix Biol 2005, 24:469-477; Iyengar P et al., J Clin Invest 2005, 115:1163-1176). Increased collagen density in the tumor stroma can promote invasion and metastasis of breast cancer cells (Lyons T R et al., Nat Med 2011, 17:1109-1115; Maskarinec G et al., Breast Cancer Res 2013, 15:R7; Kakkad S M et al., J Biomed Opt 2012, 17:116017). In fact, targeting collagen deposition in the tumor stroma can effectively reduce pulmonary metastasis in breast cancer models (Gilkes D M et al., Cancer Res 2013, 73:3285-3296; Lyons T R et al., Nat Med 2011, 17:1109-1115). In addition, differences in the organization and stiffness of the tumor stroma are known to influence tumor cell responses and stromal remodeling, a key step in metastasis (Provenzano P P et al., BMC Med 2008, 6:11-7015-6-11; Conklin M W et al., Am J Pathol 2011, 178:1221-1232; Ajeti V et al., Biomed Opt Express 2011, 2:2307-2316; Provenzano P P et al., BMC Med 2006, 4:38; Bredfeldt J S et al., J Pathol Inform 2014, 5:28-3539; Tilbury K et al., Biophys J 2014, 106:354-365; Maller 0 et al., J Cell Sci 2013, 126:4108-4110; Levental K R et al., Cell 2009, 139:891-906; Lopez J I et al., Integr Biol (Camb) 2011, 3:910-921; Conklin M W et al., Cell Adh Migr 2012, 6:249-260).
Notwithstanding the progress stated above, there is still a need for new compositions and methods for reducing cancer metastasis and local recurrence. The present invention satisfies this need.